Randomized phase III trial to compare the effectiveness of paclitaxel with that of doxorubicin in treating patients who have advanced AIDS-related Kaposi's sarcoma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether paclitaxel is more effective than doxorubicin in treating patients with advanced AIDS-related Kaposi's sarcoma

Progression-free survival [ Time Frame: Time from randomization to progression or to death from any cause, assessed up to 8 years ] [ Designated as safety issue: No ]

The group sequential method by O'Brien and Fleming for the two-sided test will be used. The significance level will be based on the type I error spending function of Lan and DeMets such that the overall significance level will be maintained at 0.05.

Secondary Outcome Measures:

Patients' health related quality of life (QOL) in terms of change in pain score, edema-related mobility, gastrointestinal (GI) symptoms and respiratory symptoms based on the total score from the Functional Assessment of HIV Infection (FAHI) v3 [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]

The relationship between the clinical benefits and the responses measured by the current Kaposi's sarcoma (KS) response criteria as well as the clinical benefits and the standard QOL assessments will be described. Difference in linear temporal trends in QOL across treatment groups compared using mixed effects linear regression models. Polynomial terms will be incorporated into the models if a linear relationship does not adequately account for the temporal trends in QOL.

Overall response rate [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]

Complete response rate [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]

Toxicities in terms of nausea/vomiting, alopecia, neuropathy and mouth sores, based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]

Patients in both arms continue treatment if there is no disease progression or unacceptable toxicity. Patients with complete response continue on study treatment for 2 courses beyond documented complete response.

Patients in both arms continue treatment if there is no disease progression or unacceptable toxicity. Patients with complete response continue on study treatment for 2 courses beyond documented complete response.

Quality of life is assessed before, during, and after treatment.

Drug: pegylated liposomal doxorubicin hydrochloride

Given IV

Other Names:

CAELYX

Dox-SL

DOXIL

doxorubicin hydrochloride liposome

LipoDox

Other: laboratory biomarker analysis

Correlative studies

Procedure: quality-of-life assessment

Ancillary studies

Other Name: quality of life assessment

Detailed Description:

PRIMARY OBJECTIVES:

I. To compare the effect of therapy with paclitaxel to therapy with liposomal doxorubicin on progression-free survival and on global assessment of quality of life of subjects with advanced AIDS-related K.S.

II. To compare the toxicity profile of intravenous paclitaxel with liposomal doxorubicin in patients with advanced AIDS-related K.S.

III. To compare the overall and complete response rate of intravenous paclitaxel with liposomal doxorubicin in patients with advanced AIDS-related K.S.

IV. To evaluate the effect of intravenous paclitaxel as compared with therapy with liposomal doxorubicin on the clinical course of HIV infection in patients with advanced AIDS-related K.S., by monitoring CD4 and CD8 lymphocyte subsets, HIV viral load and the incidence and type of opportunistic infections.

V. To explore the relationship between viral load and response to the therapy for patients with AIDS-related K.S.

VI. To describe the relationship between "technical" response as measured by the current KS response criteria and the clinical benefit of therapy as measured by the revised KS clinical benefit criteria.

OUTLINE: This is a randomized study. Patients are randomized to receive either paclitaxel (arm I) or doxorubicin HCL liposome(arm II).

Patients in both arms continue treatment if there is no disease progression or unacceptable toxicity. Patients with complete response continue on study treatment for 2 courses beyond documented complete response.

Quality of life is assessed before, during, and after treatment.

Patients are followed every 3 months for the first 2 years, then every 6 months for years 2-5, and then annually thereafter.

PROJECTED ACCRUAL: There will be 240 patients (120 patients in each arm) accrued into this study over 24 months.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Serologic diagnosis of HIV infection as documented by a positive ELISA and confirmed with a western blot, other federally approved HIV diagnostic test, or HIV viral load measurement

Biopsy-proven, measurable Kaposi's sarcoma with any of the following:

Progressive cutaneous disease

Symptomatic oropharyngeal or conjunctival lesions

Any visceral involvement

Tumor-related lymphedema

Tumor-related ulceration or pain

NOTE: All patients must have measurable disease; baseline measurements must be obtained < 4 weeks prior to registration

ECOG performance status 0-2

ANC >= 1000/mm³ (with or without the use of colony-stimulating factors)

Platelet count >= 50,000/mm³

Hemoglobin >= 8 gm/dL

Bilirubin < 1.5 x the upper limit of normal (unless elevation is due to Crixivan administration with isolated elevation in conjugated bilirubin)

SGOT or SGPT =< 5 x the upper limit of normal

Creatinine =< 2.1 mg/dl

Women must not be pregnant or lactating due to potential toxicity of therapy

Women of childbearing potential and sexually active men must be advised to use an accepted and effective method of contraception due to potential toxicity of therapy

No prior systemic cytotoxic chemotherapy for Kaposi's sarcoma

Prior radiation therapy must have been discontinued >= 7 days prior to randomization and must NOT have been delivered to marker lesions; (NOTE: Radiation therapy will not be permitted during study treatment)

No active, untreated infection (no new opportunistic infectious complications within the previous week requiring a change in antibiotics); maintenance therapy for opportunistic infections will be allowed

No prior or concomitant malignancy other than curatively treated carcinoma in situ of the cervix or basal/squamous cell carcinoma of the skin

No neuropsychiatric history or altered mental status that might prevent informed consent or affect the ability of the patient to comply with the study

Institutions must ask patients to participate in the quality of life portion of the protocol; however, patients may decline participation in this component of the study and still be eligible; the reason for refusal or inability to complete the QOL assessments must be documented in the Assessment Compliance Form (#596)

Patients must be on stable (no change in drugs or doses) antiretroviral therapy for greater than 14 days prior to study; a combination regimen is required; ideally this will be a protease inhibitor containing triple therapy regimen

Patients must give signed, written informed consent

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00003350